Because of the tremendous impact of hyperproliferative diseases such as cancer on an ever-growing world population, there are a plethora of treatment methods that are as varied as the many different types of cancer. While general chemotherapeutic treating regimens can sometimes be effective in controlling certain types of cancer, their side effects often render them distasteful or unendurable by patients. These general chemotherapeutic treatment regimens typically take much the same form as other therapeutic/pharmaceutical delivery methods for severe illnesses, e.g., oral, intravenous, parenteral, etc. However, the fact that such delivery methods result in a widespread cellular toxicity, which is the major cause of many undesirable side effects, is a problem with conventional chemotherapy.
This down side of conventional chemotherapeutic cancer treatments can be minimized by using delivery mechanisms that specifically target cancer cells or certain hyperfunctionalities associated with malignancy, e.g., increased blood flow, increased vascularization, increased replicative function/hyperproliferation, increased selective cellular transport, etc. Many publications describe specific types of compounds (drugs) that seek out specific cells or areas having increased or decreased cellular functions specific to malignancies. Many other publications describe modified compounds, or prodrugs, in which an active compound is rendered temporarily inactive and chemically attached to a moiety (or group of moieties) designed to seek out specific cells or areas having increased or decreased cellular functions specific to malignancies, and designed to re-activate the compound at the desired time/location in vivo. Still other publications describe the use of physically sequestered compounds, e.g., time-release dosage forms, degradable drug reservoirs, pH-activated gate devices, multi-reservoir implantable chips, or the like, for treating cancer. Nevertheless, all of these methods rely on long-distance targeting, i.e., using seeker molecules that travel through the body until they find their target, only then unloading their treatment payload.
Cancers related to the skeletal system can be difficult to treat with conventional chemotherapy. For these types of cancers, an in situ treatment mechanism is needed for releasing active agents that need not be target-specific to avoid the widespread side effects of traditional chemotherapy, due to an immediate in vivo proximity to the malignant cells by virtue of in situ implantation.
Implants for treating/fixing bone injuries/deformities are well known. But because bones and orthopedic implants are essentially intermediate-term scaffolds (often load bearing, but designed to biodegrade slowly to allow bone to regrow around them/in their place), they have been utilized mostly for structural purposes. Further, while the surface characteristics of orthopedic implants have been often altered, that alteration has typically been for purposes of mechanical stability and/or biocompatibility. To the extent that there have been prior publications on active agent-loaded implantable materials, those publications have largely involved soft tissue or organs, and have largely centered on treatment of different maladies/diseases/conditions.
The present invention, as described below, offers several unique solutions to the problems and difficulties previously described.